POS0538 PREDICTING VALUE OF CIRCULATING SEMAPHORIN 4A FOR RHEUMATOID ARTHRITIS PROGRESSION
Authors: J. Avouac, E. Vandebeuque, A. Combier, L. Poiroux, A. Steelandt, M. Boisson, V. Gonzalez, A. Cauvet, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2022)

Background The lack of validated tools to predict rheumatoid arthritis (RA) disease course warrants the development of new reliable biomarkers. We have previously detected increased SEMA4A expression in endothelial cells, synovial tissue, and serum of patients with RA. In addition, SEMA4A serum levels correlated with multiple clinical, biological, and power doppler ultrasound markers of disease activity and angiogenesis (1). Objectives To evaluate the merit of circulating semaphorin 4A (SEMA4A) for the prediction of disease progression in RA patients. Methods Prospective monocentric observational study including consecutive RA patients between May 2016 and February 2018 with available SEMA4A concentrations, measured by quantitative ELISAs (Coud-Clone Corp, Katy, TX). Increased SEMA4A concentrations were defined as values &gt;94 ng/mL, as previously reported ( 1 ). Patients were followed up on an annual basis until August 2021. Primary endpoints were the occurrence of patient-reported flares with swollen joints and the necessity to initiate or change a targeted biologic or synthetic disease-modifying anti-rheumatic drugs. Results A total of 101 patients (85 females, 84%) were included, with a mean age of 58±13 years and a mean disease duration of 14±11 years. During a follow-up period of 41±15 months, disease flares occurred in 38 patients and targeted therapy was added or modified in 26 patients because of insufficient disease control. Increased baseline SEMA4A levels were predictive of flares and treatment escalation (hazard ratio, HR: 2.43, 95% confidence interval, CI 1.27-4.68 and 2.73, 95%CI 1.24-5.96, respectively) (Figure 1 A-B ). Multivariate Cox analyses confirmed that SEMA4A was an independent predictors of flares and treatment escalation (HR: 2.12, 95%CI 1.04-4.32 and 2.71, 95%CI1.14-6.43, respectively), and revealed that DAS28-CRP and synovial hyperhemia were independent predictors of flares. Baseline age, disease duration, ACPA or RF positivity, smoking status, presence of erosions, line of targeted DMARDs, treatment with corticosteroids and CRP levels were not predictive of these outcomes. SEMA4A remained predictive of flares and treatment escalation in the 58 patients with a DAS28 &lt;3.2 at baseline (HR: 3.68, 95%CI 1.33-10.17 and 3.50, 95%CI 1.02-12.01, respectively). Baseline SEMA4A levels also identified more active and difficult to treat patients who maintained higher mean DAS28-CRP values during the follow-up period (Figure 1 C ). The highest predictive value of flares and treatment escalation was obtained with the combination of increased circulating SEMA4A and/or DAS28-CRP&gt;3.2 and/or the presence of synovial hyperemia on power-doppler ultrasound (HR:4.88, 95%CI 1.50-15.89 and 10.42, 95%CI 1.41-76.94, respectively). Figure 1. A-C: Predictive value of SEMA4A for the progression of rheumatoid arthritis. A, Disease flare-free survival according to circulating SEMA4A concentrations (≤ or &gt; 94 ng/mL). B, Time to treatment escalation according to circulating SEMA4A concentrations (≤ or &gt; 94 ng/mL). C, Course of the DAS28-CRP during the follow-up period according to baseline SEMA4A concentrations (≤ or &gt; 94 ng/mL). All data are shown as the mean ± SEM. * p&lt;0.05, ** p&lt;0.01 and *** p&lt;0.001, determined by Student’s t test. Conclusion Circulating SEMA4A was a robust biomarker of disease progression in this cohort, complementary of the DAS28 and synovial hyperemia on power-doppler ultrasound. These results need to be confirmed in replication cohorts. References [1] Avouac et al, Arthritis Rheumatol 2021 Disclosure of Interests None declared.